This chapter deals primarily with APGO Educational Topic Area:
TOPIC 31 FETAL GROWTH ABNORMALITIES
Students should be able to list the various fetal growth abnormalities, discuss possible etiologies, and describe possible complications. They should be able to outline a basic approach to evaluation and management of fetal growth abnormalities.
Clinical Case
A 26-year-old G2P1001 female has been receiving routine prenatal care. Her previous pregnancy and delivery were uncomplicated. She is of average height and weight. When seen for her visit at a well-dated gestational age of 29 weeks, her fundal height is noted to be 24 cm, which is less than the 28 to 29 cm you would expect at this time. Fetal heart tones are normal. Based on the fact that her uterine size is less than the expected for her gestational age, you suspect intrauterine growth restriction (IUGR). Such a situation as described is reasonably common in obstetrics, and care providers must have a good understanding of the possible etiologies and management of patients with IUGR. Likewise, an estimated fetal size and weight significantly above that expected poses additional challenges for those caring for such patients.
INTRAUTERINE GROWTH RESTRICTION
“Fetal growth restriction” describes infants whose weights are much lower than expected. Population-based norms are used to categorize abnormal growth (Table 14.1). A fetus or infant whose weight is less than the 10th percentile of a specific population at a given gestational age is designated as having intrauterine growth restriction (IUGR). Therefore, careful assignment of gestational age is crucial to the diagnosis and management of patients with IUGR.
The term small for gestational age (SGA) is used to describe an infant with a birth weight at the lower extreme of the normal birth weight distribution. In the United States, the most commonly used definition of SGA is a birth weight below the 10th percentile for gestational age. The use of the terms “small for gestational age” and “intrauterine growth restriction” has been confusing, and the terms are often used interchangeably. In this chapter, SGA will be used only in reference to the infant and IUGR to the fetus.
The use of gestational age percentiles remains limited for a number of reasons. First, by definition, the prevalence of IUGR will be 9%, but not all such neonates are pathologically small. Second, any percentile cutoff fails to take into account an individual’s growth potential. Also, a simple percentile cannot take into account growth rate. The change in percentile over time or change in specific measurements may be more important. Finally, the time when the growth restriction is found may be a factor in morbidity and mortality: growth restriction at earlier gestational ages has greater effects on morbidity and mortality.
Significance
The goal of recognizing neonates with growth abnormalities is to identify infants at risk for increased short-term and long-term morbidity or mortality. In the short term, the growth-restricted fetus potentially lacks adequate reserves to continue intrauterine existence, to undergo the stress of labor, and to fully adapt to neonatal life. These conditions make the infant vulnerable to intrauterine fetal death, asphyxia, acidemia, and intolerance to labor. Neonatal complications include low Apgar scores, polycythemia, hyperbilirubinemia, hypoglycemia, hypothermia, apnea, respiratory distress, seizures, sepsis, meconium aspiration, and neonatal death.
Alterations in fetal growth may have lifelong implications. The antenatal response or fetal adaptation to the intrauterine nutritional and metabolic environment may predict or dictate the response to an extrauterine environment. Increasing evidence supports the concept of fetal origins for adult diseases and the association between birth size and long-term health. Associations have been reported between birth weight and adult obesity, cardiovascular disease (e.g., coronary heart disease, hypertension, and stroke), insulin resistance, and dyslipidemia. Therefore, intrauterine growth may reflect the foundation of many aspects of lifelong physiologic function.
In general, the smaller the fetus with IUGR, the greater its risk for morbidity and mortality. Perinatal morbidity and mortality are significantly increased, especially with weights below the third percentile for gestational age. One study found that 26% of all stillbirths were SGA. Thus, it is important to identify such infants in utero so that management maximizes the quality of their intrauterine environment, permits planning and implementation of delivery using the safest means possible, and provides necessary care in the neonatal period.
Pathophysiology
For a fetus to thrive in utero, an adequate number of fetal cells and cells that differentiate properly are both requisite. In addition, nutrients and oxygen must be available via an adequately functioning uteroplacental unit to allow an increase in the number of cells and in cell size. Early in pregnancy, fetal growth occurs primarily through cellular hyperplasia, or cell division, and early-onset IUGR may lead to an irreversible diminution of organ size and, perhaps, function. Early-onset IUGR is also more commonly associated with genetic factors, immunologic abnormalities, chronic maternal disease, fetal infection, and multiple pregnancies. Later in pregnancy, fetal growth depends increasingly on cellular hypertrophy rather than hyperplasia alone, so that delayed-onset IUGR may also result in decreased cell size, which may be more amenable to restoration of fetal size with adequate nutrition. The normal fetus grows throughout the pregnancy, but the rate of growth decreases after 37 weeks of gestational age as the fetus depletes fat for cellular growth.
The placenta grows early and rapidly compared with the fetus, reaching a maximum surface area of about 11 m2 and weight of 500 g at approximately 37 weeks of gestational age. Thereafter, there is a slow but steady decline in placental surface area (and, hence, function), primarily because of microinfarctions of its vascular system. Late-onset growth restriction may, therefore, be primarily related to decreased function and nutrient transport of the uteroplacental unit, a condition termed uteroplacental insufficiency. In addition, because there is a close relationship between placental surface area and fetal weight, factors that act to decrease placental size are also associated with decreased, that is, restricted, growth.
Etiology
IUGR is a descriptive term for a condition that has numerous potential causes. Determining the specific diagnosis is important for optimal management. Although a number of causes of IUGR have been recognized, a definite etiology of IUGR cannot be identified in approximately 50% of all cases. In addition, because the utilization of a percentile cutoff of 10% alone will result in a high proportion of false positives, two thirds or more of such fetuses categorized as IUGR will be simply constitutionally small and otherwise healthy.
Factors that affect fetal growth are extensive and include maternal, fetal, and placental causes; these are listed in Box 14.1.
BOX 14.1 Risk Factors Associated with Intrauterine Growth Restriction
• Maternal medical conditions
• Hypertension
• Renal disease
• Restrictive lung disease
• Diabetes (with microvascular disease)
• Cyanotic heart disease
• Antiphospholipid syndrome
• Collagen vascular disease
• Hemoglobinopathies
• Smoking and substance use and abuse
• Severe malnutrition
• Primary placental disease
• Multiple gestation
• Infections (viral and protozoal)
• Genetic disorders
• Exposure to teratogens
American College of Obstetricians and Gynecologists. Intrauterine Growth Restriction. ACOG Practice Bulletin 12. Washington, DC: American College of Obstetricians and Gynecologists; 2000:2.
Maternal Factors
Maternal factors associated with IUGR include viral infections, such as rubella, varicella, and cytomegalovirus, which are associated with high rates of growth restriction, particularly if infection occurs early in pregnancy. Although these infections may manifest in the mother only as mild “flu-like” illnesses, injury to the fetus during organogenesis can result in a decreased cell number, resulting in diminished growth with or without multiple congenital anomalies. However, 5% or fewer of all cases of IUGR are related to early infection with these or other viral agents. Maternal substance abuse affects fetal growth, and almost all infants with fetal alcohol syndrome will be growth restricted. Women who smoke during pregnancy deliver babies 200 g smaller on average than do women who do not smoke; moreover, the rate of growth restriction is three- to fourfold greater among babies born to women who smoke during pregnancy. Women who use narcotics, heroin, methadone, or cocaine also have rates of growth-restricted babies ranging from as much as 30% to 50%. Medications known to be associated with IUGR include anticonvulsant medications, warfarin, and folic acid antagonists. Altitude may also affect fetal growth.
Other maternal factors that affect fetal growth and body composition include demographic factors and medical conditions. Extremes in maternal age (age younger than 16 years and older than 35 years) are associated with an increased risk of fetal growth restriction. Medical conditions that alter or affect placental function may also be causative factors.
Although one common pathway has not been clearly identified, many of these disorders occur together. Women with a history of prior obstetric complications have an increased risk of growth abnormalities. Maternal metabolism and body composition are two of the strongest regulators of fetal growth. Nutritional deficiencies and inadequate weight gain, particularly in teens or in underweight women, may result in IUGR.
Fetal Factors
The inherent growth potential of the individual is determined genetically. Female fetuses are at greater risk for IUGR than males. In addition, up to 5% of growth-restricted fetuses have a chromosomal abnormality, a number that rises to 20% if both IUGR and mental retardation are present. In addition, single-gene mutations, such as the glucokinase gene mutation, and structural malformations, such as gastroschisis and renal agenesis, can also result in abnormalities of growth. Finally, multifetal pregnancies are at increased risk for growth restriction.
Placental Factors
The placenta is critical for nutrient regulation and transportation from mother to fetus. Abnormalities in placentation or defective trophoblast invasion and remodeling may contribute to fetal growth restriction as well as other disorders of pregnancy. In addition, uterine anomalies (uterine septum or fibroids) may limit placental implantation and development and, consequently, nutrient transport, resulting in inadequate nutrition for the developing fetus. Finally, the genetic composition of the placenta is important, and abnormalities such as confined placental mosaicism are associated with growth delay.
Diagnosis
Assessment of gestational age is critically important in early pregnancy, because dating becomes increasingly imprecise as gestational age advances. Antenatal recognition of IUGR depends upon the recognition of risk factors and the clinical assessment of uterine size, followed by biometric measurements.
Physical Examination
Physical examination is limited in usefulness in recognizing IUGR or in making a specific diagnosis, but it is an important screening test for abnormal fetal growth. Maternal size and weight gain throughout pregnancy also have limited value, but access to such information is readily available; a low maternal weight or little or no weight gain during pregnancy may suggest IUGR. Serial measurements of fundal height are commonly used as a screening test for IUGR but have high rates of false-negative and false-positive predictive values. Between 20 and 36 weeks of gestation, fundal height should increase approximately 1 cm/week, consistent with gestational age in weeks (Fig. 14.1). A discrepancy may be related to constitutional factors, but a significant discrepancy of more than 2 cm may indicate IUGR and the need for an ultrasound examination. Clinical estimations of fetal weight alone are not helpful in diagnosing IUGR, except when fetal size is grossly diminished.
FIGURE 14.1. Fundal height evaluation as a screening test for intrauterine growth restriction. p, percentile. (Reprinted with permission from Scott JR, Di Saia PJ, Hammond CB, et al. Danforth’s Obstetrics and Gynecology. 8th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 1999.)
Ultrasonography
If IUGR is suspected based on risk factors and/or clinical assessment, ultrasonography should be performed to assess fetal size and growth. Specific fetal biometry measurements are compared with standardized tables that reflect normal growth at a certain gestational age. The four standard fetal measurements include the 1) biparietal diameter, 2) head circumference, 3) abdominal circumference (AC), and 4) femur length. Conversion of individual morphologic measurements to fetal weight using published equations or ratios of measurements can provide useful estimations of fetal size. An AC within the normal range reliably excludes growth restriction, with a false-negative rate of less than 10%. A small AC or fetal weight estimate below the 10th percentile suggests the possibility of growth restriction, with the likelihood increasing as the percentile rank decreases.
Direct Studies
Direct invasive studies of the fetus are useful in selected patients with IUGR. Amniocentesis for fetal lung maturity may assist delivery planning near term or when there is uncertainty regarding gestational age and concern for growth restriction. Fetal karyotyping and viral cultures and polymerase chain reactions can be performed on fluid obtained by amniocentesis. Rarely, chorionic villus sampling (biopsy of placenta) or direct blood sampling (percutaneous umbilical blood sampling) may be necessary for specific studies.
Doppler Velocimetry
Doppler velocimetry of fetal vessels provides further insight into the fetal response to altered growth and has become part of the standard assessment of the fetus once IUGR is diagnosed. Doppler velocimetry has been shown to both reduce interventions and improve fetal outcome in pregnancies at risk for IUGR. Fetal–placental circulation is evaluated in the umbilical artery and is measured by a systolic/diastolic (S/D) ratio. The S/D indirectly measures impedance or resistance downstream within the placental vessels. As placental resistance increases, diastolic flow decreases and the S/D ratio rises. A normal S/D ratio at term is 1.8 to 2.0. Fetuses with IUGR with absent or reversed diastolic flow have progressively worse perinatal outcomes (Fig. 14.2). The fetal middle cerebral artery is also evaluated and reflects fetal adaptation. The pathophysiologic response to reduced placental perfusion generally spares the fetal brain, resulting in an increase of diastolic and mean blood flow velocity in the middle cerebral artery. Ductus venosus may also be evaluated by Doppler ultrasound, and the fetus with abnormal ductus flow is at very high risk of adverse outcome.
FIGURE 14.2. Doppler velocimetry. Umbilical artery Doppler of a 35-week fetus demonstrates an elevated S/D ratio of 3.76 (arrowhead, calipers) due to diminished diastolic flow. (From Doubilet PM, Benson CB. Atlas of Ultrasound in Obstetrics and Gynecology. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:227.)
Management
The goal of management of a growth-restricted fetus is to deliver the healthiest possible infant at the optimal time. Continued management of pregnancy with IUGR is based on the results of fetal testing. Serial evaluations of fetal biometry should be performed every 3 or 4 weeks to follow the extent of growth restriction. Fetal surveillance is important and may include fetal movement counting, nonstress testing, biophysical profiles, and Doppler studies. There are no specific therapies that have proven beneficial for pregnancies complicated by IUGR.
The fetus should be delivered if the risk of fetal death exceeds that of neonatal death, although in many cases these risks are difficult to assess. For example, a fetus with IUGR with normal anatomic survey, normal amniotic fluid volume, normal Doppler studies, and normal fetal testing may not benefit from early delivery. Conversely, the growth-restricted fetus with serial biometry measurements documenting decreasing growth rate and/or mildly abnormal Doppler studies may benefit from delivery, with or without fetal maturity documentation. These decisions must be made while considering the gestational age of the fetus and the known risks associated with prematurity.
Neonatal Management
Neonatal management of IUGR infants, which is partially dependent on gestational age, includes preparation for neonatal respiratory compromise, hypoglycemia, hypothermia, and hyperviscosity syndrome. Growth-restricted fetuses have less fat deposition in late pregnancy, so newborn euglycemia cannot be maintained by the normal mechanism of mobilization of glucose by fat metabolism. Hyperviscosity syndrome results from the fetus’s attempt to compensate for poor placental oxygen transfer by increasing the hematocrit to more than 65%. After birth, this marked polycythemia can cause multiorgan thrombosis, heart failure, and hyperbilirubinemia. Overall, growth-restricted infants who survive the neonatal period have a generally good prognosis.
MACROSOMIA
Two terms have been used to define excessive fetal growth. Fetal macrosomia is based on weight alone and refers to a very large fetus, typically with an estimated weight of greater than 4,000 to 4,500 g or more. There is no general agreement among obstetricians on the precise definition of macrosomia. However, morbidity increases sharply with birth weights ≥4,500 g when compared with the general population; thus, 4,500 g is often used as an estimate above which a fetus is considered macrosomic. Large for gestational age (LGA) generally implies a birth weight of >90% for a given gestational age and is dependent on both weight and gestational age with percentiles generated from population-specific norms (see Table 14.1). By definition, the prevalence of LGA is fixed, but not all neonates at the upper extreme of size are pathologically large. Growth potential, growth rate, and gestational age at onset may be important considerations.
Etiology
Macrosomia, like fetal growth restriction, has multiple potential causes, categorized into fetal or maternal factors (Box 14.2).
Maternal Factors
Maternal factors include a history of macrosomia, maternal prepregnancy weight, weight gain during pregnancy, multiparity, male fetus, gestational age greater than 40 weeks, ethnicity, maternal birth weight, maternal height, maternal age younger than 17 years, and a positive 50-g glucose screen with a negative result on the 3-hour glucose tolerance test.
BOX 14.2 Risk Factors for Large for Gestational Age
Fetal
Genetic potential
Specific gene disorders
Male sex
Maternal
History of previous macrosomic pregnancy
Metabolism
Body composition
Pregnancy weight gain
Parity
The magnitude of glucose intolerance during pregnancy and specific measures of control are correlated with fetal weight and fetal fat mass. Lipids are also associated with fetal size, with triglycerides and free fatty acids positively correlated to birth weight, and triglycerides independently associated with LGA infants. Maternal body composition and body mass index are major determinants of insulin sensitivity, independent of hypertension and pregestational or gestational diabetes. Also, maternal weight gain and pregravid weight contribute to the variance in fetal birth weight. Finally, increased parity is associated with larger babies.
Fetal Factors
Similar to fetal growth restriction, fetal factors include the genetic composition or inherent growth potential of the individual and genetic syndromes such as Beckwith-Wiedemann syndrome. Male fetuses are also more commonly affected than female fetuses.
Significance
Macrosomia is associated with both increased maternal and fetal/neonatal risks. Because of labor abnormalities, a patient with a macrosomic fetus has an increased risk of cesarean delivery. The risks of postpartum hemorrhage and vaginal lacerations are also elevated with macrosomia. Maternal infections associated with macrosomia include urinary tract infection in women undergoing elective caesarean section and puerperal fever in women undergoing a trial of labor. Risks to the fetus are shoulder dystocia and fracture of the clavicle, although brachial plexus nerve injury is rare. Macrosomic infants also have an increased risk of lower Apgar scores.
Other neonatal risks are partially dependent on the underlying etiology of macrosomia, such as maternal obesity or diabetes, and may include an increased risk of hypothermia, hyperbilirubinemia, hypoglycemia, prematurity, and stillbirth. The relationship between gestational age and fetal size is important. Macrosomic preterm infants remain at risk for complications of prematurity. The size and extent of maturity are independent. Long-term risks include overweight or obesity in later life, again illustrating that intrauterine growth may predict the foundation of many aspects of lifelong physiologic function.
Diagnosis
The diagnosis of macrosomia is based on estimated fetal weight above the 90th percentile for gestational age. Assessment of pregnancy duration becomes increasingly imprecise at later gestational ages, so careful dating of pregnancy as early as possible is important. The two primary methods for clinical estimation of fetal weight are Leopold maneuvers (abdominal palpation; see Fig. 9.7) and measurement of the height of the uterine fundus above the maternal symphysis pubis. Measurement of the symphysis– fundal height alone is a poor predictor of fetal macrosomia and should be combined with clinical palpation (Leopold maneuvers) to be useful.
Clinical findings may be combined with ultrasound to diagnose macrosomia. Ultrasound-derived estimates of fetal weight are obtained by entering the measurements of various fetal body parts, usually including the AC, into one of several popular regression equations. However, most of the regression formulas currently in use are associated with significant errors when the fetus is macrosomic. The superiority of ultrasound-derived estimates of fetal weight over clinical estimates has not been established.
The true value of ultrasound in management of macrosomia is its ability to rule out the diagnosis.
The differential diagnosis of an enlarged uterus includes a large fetus, more than one fetus (multiple gestation), extra amniotic fluid (polyhydramnios), large placenta (molar pregnancy), and large uterus (uterine leiomyomata, other gynecologic tumor, or uterine anomaly).
Management
For mothers without diabetes, no clinical interventions designed to treat or curb fetal growth when macrosomia is suspected have been reported. Current evidence does not support early delivery for macrosomia alone, because induction of labor does not decrease maternal and neonatal morbidity; however, it does increase the rate of cesarean deliveries. In addition, the data do not support a specific estimated fetal weight at which women should undergo elective cesarean delivery. Given the limitations of ultrasound estimations and the association with increasing injury with increasing infant weight, the American College of Obstetricians and Gynecologists recommends that a cesarean delivery should be offered for estimated fetal weights greater than 5,000 g in women without diabetes and greater than 4,500 g in women with diabetes.
Various techniques can be used to facilitate vaginal delivery in the case of shoulder dystocia, such as exaggerated flexion of the thighs (McRoberts maneuver; see Fig. 9.9A), suprapubic pressure, various rotations, episiotomy, delivery of the posterior arm, and intentional clavicular fracture. The Zavanelli maneuver, cephalic replacement with subsequent cesarean delivery, has yielded mixed results. A prolonged second stage of labor or arrest of descent in the second stage is an indication for cesarean delivery. Postpartum or neonatal management depends on gestational age and underlying etiology.
Clinical Follow-Up
You should share your concerns about possible intrauterine growth restriction with your patient. Ultrasound evaluation is warranted. Once the diagnosis is established, careful, ongoing management of your patient throughout her pregnancy and delivery is important. Frequent counseling and addressing your patient’s questions and concerns is also important. Caring for patients with fetal growth abnormalities, whether “too small” or “too big,” can be challenging.
thePoint Visit http://thepoint.lww.com/activate for an interactive USMLE-style question bank and more!